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基于 3D 生物打印 Gel/dECM/Qcs 复合支架修复糖尿病足溃疡的研究。

Investigation on repairing diabetic foot ulcer based on 3D bio-printing Gel/dECM/Qcs composite scaffolds.

机构信息

Dalian Medical University, Dalian, Liaoning, 116011, China; Department of Hand and Foot Microsurgery, Dalian Municipal Central Hospital Affiliated of Dalian University of Technology, Dalian 116033, China.

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.

出版信息

Tissue Cell. 2023 Dec;85:102213. doi: 10.1016/j.tice.2023.102213. Epub 2023 Sep 1.

Abstract

Diabetic foot ulcers are one of the most serious of the numerous complications of diabetes mellitus, causing great physical trauma and financial stress to patients, and accelerating wound healing in diabetic patients remains one of the major clinical challenges. Exosomes from adipose-derived stem cells can directly and indirectly promote wound healing. However, due to the low retention rate of exosomes in the wound, exosome treatment is difficult to achieve the expected effect. Therefore, it is of great significance to synthesize a composite scaffold that can stably load exosomes and has antibacterial properties. In this study, fresh pig skin was decellularized to obtain decellularized matrix (dECM). Secondly, quaternized chitosan (Qcs) was modified with quaternary ammonium salt to make it soluble in water after quaternization. Finally, Gel-dECM-Qcs (GDQ) bioink was prepared by adding acellular matrix and quaternized chitosan with temperature sensitive gelatin (Gel) as carrier. Tissue engineered composite scaffolds were then prepared by extrusion 3D printing technology. Subsequently, the physicochemical properties, biocompatibility and antimicrobial capacity of the composite scaffolds were determined, and the data showed that the composite scaffolds had good mechanical properties, biocompatibility and antimicrobial capacity, and the maximum stress of the composite scaffolds was 1.16 ± 0.05 MPa, the composite scaffolds were able to proliferate and adhered to the L929 cells, and the kill rates of composite scaffolds against E. coli and S. aureus after incubation for 24 h were 93.24 ± 1.22 % and 97.34 ± 0.23 %, respectively. Overall, the GDQ composite scaffolds have good mechanical properties adapted to skin bending, its good biocompatibility can promote the growth and migration of fibroblasts, reshape injured tissues, accelerate the wound healing, and excellent antimicrobial ability can inhibit the growth of E. coli and S. aureus, reducing the impact of bacterial infections on wounds. Moreover, the composite scaffolds have the potential to be used as exosom-loaded hydrogel dressings, which provides a basis for the subsequent research on the repair of diabetic foot ulcers.

摘要

糖尿病足溃疡是糖尿病众多并发症中最严重的一种,给患者造成巨大的身体创伤和经济压力,加速糖尿病患者的伤口愈合仍然是临床面临的主要挑战之一。脂肪源性干细胞来源的外泌体可以直接和间接促进伤口愈合。然而,由于外泌体在伤口中的保留率低,外体治疗很难达到预期的效果。因此,合成一种能稳定负载外泌体且具有抗菌性能的复合支架具有重要意义。本研究采用新鲜猪皮脱细胞法制备脱细胞基质(dECM)。其次,壳聚糖(Qcs)经季铵化改性后,季铵化后可溶于水。最后,以温度敏感型明胶(Gel)为载体,加入脱细胞基质和季铵化壳聚糖制备 Gel-dECM-Qcs(GDQ)生物墨水。然后通过挤出 3D 打印技术制备组织工程复合支架。随后,对复合支架的理化性能、生物相容性和抗菌能力进行了测定,结果表明复合支架具有良好的机械性能、生物相容性和抗菌能力,复合支架的最大应力为 1.16±0.05 MPa,复合支架能够增殖并黏附于 L929 细胞,复合支架孵育 24 h 后对大肠杆菌和金黄色葡萄球菌的杀灭率分别为 93.24±1.22%和 97.34±0.23%。总之,GDQ 复合支架具有良好的机械性能,适应皮肤弯曲,良好的生物相容性可促进成纤维细胞的生长和迁移,重塑受损组织,加速伤口愈合,优异的抗菌能力可抑制大肠杆菌和金黄色葡萄球菌的生长,减少细菌感染对伤口的影响。此外,复合支架具有作为负载外泌体的水凝胶敷料的潜力,为随后研究糖尿病足溃疡的修复提供了依据。

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